- "One function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. It is also a recruiter of several chromatin remodeling enzymes such as methylases and acetylases.
pRb belongs to the pocket protein family, whose members have a pocket for the functional binding of other proteins. Should an oncogenic protein, such as those produced by cells infected by high-risk types of human papillomaviruses, bind and inactivate pRb, this can lead to cancer."
REPORTEDLY THIS EFFECT OF Rb GENE GO THROUGH CDKs
Cyclin-dependent kinases (CDKs) play essential roles in cell proliferation and gene expression. Although distinct sets of CDKs work in cell division and transcription by RNA polymerase II (Pol II), they share a CDK-activating kinase (CAK), which is itself a CDK-Cdk7-in metazoans."FISHER ET AL
- cholera toxin - increase cAMP levelsIn a cAMP-dependent pathway, the activated Gs alpha subunit binds to and activates an enzyme called adenylyl cyclase, which, in turn, catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP). Increases in concentration of the second messenger cAMP may lead to the activation of
- cyclic nucleotide-gated ion channels
- exchange proteins activated by cAMP (EPAC) such as RAPGEF3
- an enzyme called protein kinase A (PKA).
- enzymes that convert glycogen into glucose
- enzymes that promote muscle contraction in the heart leading to an increase in heart rate
- transcription factors, which regulate gene expression
(cyclin-dependent kinase 7 (CDK7) has essential roles in both the cell-division cycle and transcription, as a CDK-activating kinase (CAK) and as a component of the general transcription factor TFIIH,") FISHER
Cyclic AMP inhibits the proliferation of thyroid carcinoma cell lines through regulation of CDK4 phosphorylation.(Rocha)
Rb inactivation in cell cycle and cancer: the puzzle of highly regulated activating phosphorylation of CDK4 versus constitutively active CDK-activating kinase.(Paternot et al!)
LINKING cyclic-AMP to Rb
activators of c-AMPPaternot S, Bockstaele L,
- forskolin - a diterpene natural product that activates adenylyl cyclase
- caffeine and theophylline inhibit cAMP phosphodiesterase, which leads to an activation of G proteins that result in the activation of the cAMP pathway
- bucladesine (dibutyryl cAMP, db cAMP) - also a phosphodiesterase inhibitor
- pertussis toxin, which increase cAMP levels by inhibiting Gi to its GDP (inactive) form. This leads to an increase in adenylyl cyclase, therefore increasing cAMP levels, which can lead to an increase in insulin and therefore hypoglycemia (WIKIPEDIA)
take Theophylline for that matter!
DO NOT DRINK COFFEE WITH MTORC1 DRIVEN CONDITION?
YOU BE THE JUDGE!